Repeat liver resection for recurrent colorectal liver metastases

BACKGROUND: This study aimed to delineate the role of surgery for recurrent colorectal cancer in the liver and to identify prognosticators for better patient selection and outcome. METHODS: Data from 90 repeat hepatectomies (second = 75; third = 12; fourth = 3) for recurrent colorectal cancer were collected. RESULTS: After the second hepatectomy, the 3-and 5-year survival rates were 48% and 31%, respectively. Twenty-seven percent (20 of 75) of patients are alive without recurrence after a median follow-up of 27 months, and 9 survived more than 5 years. Four or more tumors, positive regional lymph node metastases, concomitant extrahepatic disease, and residual tumor were independent poor prognostic factors after the second hepatectomy. CONCLUSIONS: Repeat hepatectomy should be applied for recurrent colorectal cancer, when curative removal of the tumor is possible, although the benefit from treatment was limited in a patient with regional lymph node metastases, 4 or more metastases, or extrahepatic disease.     

Reduction of tumorigenicity by an interferon-γ-gene-transduced tumor on another syngeneic tumor in a murine model

To evaluate the effect of interferon-γ-genetransduced cells, DS mice were inoculated into their footpads with syngeneic mammary adenocarcinoma SC42 admixed with interferon-γ producing mammary adenocarcinoma SC115Kγ, which had been established by an interferon-γ-gene transduction in another syngeneic mammary adenocarcinoma SC115 using retroviral vectors. These mice rejected both tumor cells and developed resistance to subsequent challenges with either SC115 or SC42 cells inoculated into their opposite posterior footpads. These results thus indicate that systemic immunological memory to each of the independent tumor cell lines developed in these mice. Although the SC42 cells admixed with irradiated SC115Kγ cells were rejected by these mice, the SC42 cells admixed with irradiated SC115neoR, in which the neo-gene had been transduced, were observed to proliferate. Tumor rejection was reversed by an in vivo administration of anti-interferon-γ antibody, thus suggesting that locally produced interferon-γ plays an important role in tumor elimination and immunological memory induction. In conclusion, interferon-γ-gene-transduced tumor cells are therefore considered to have a therapeutic potential for other types of malignant tumor cell lines.     

Clinical, immunological and MRI features of myelitis with atopic dermatitis (atopic myelitis)

In order to clarify the characteristic features of myelitis with atopic dermatitis (AD), we compared the clinical, immunological and MRI findings between 14 myelitic patients with AD and 12 myelitic patients without AD. The myelitic patients with AD showed the following distinct features, compared with those without AD. (1) A preferential involvement of the cervical cord, as shown by neurologic as well as MRI examinations (14/14 vs. 5/12; P=0.0012), (2) paresthesia/dysesthesia as the predominant symptoms and a rare occurrence of definite muscle weakness (0/14 vs. 5/12; P=0.0120) and dysuria (1/14 vs. 8/12; P=0.0029), (3) a lower Expanded Disability Status Scale score (mean, 1.5 vs. 3.5; P=0.0018), (4) normal cerebrospinal fluid (CSF) findings including those for the IgG index and oligoclonal IgG bands and (5) a persistence of neurologic symptoms and MRI lesions during the follow-up periods (mean, 17 months). In addition, both the serum total IgE level and the frequency of specific IgE to Dermatophagoides farinae were significantly higher in the myelitic patients with AD (median IgE=1266 U/ml, specific IgE 14/14) than in those without AD (145 U/ml, P=0.0034 and 8/12, P=0.0331, respectively) and in 40 healthy controls (86 U/ml, P<0.0001 and 12/40, P<0.0001, respectively). Since myelitis with AD has distinct features and atopy to mite antigens appears to be the underlying cause of this condition, it may therefore be a distinct subtype of myelitis.     

Glomerular hypertrophy in preeclamptic patients with focal segmental glomerulosclerosis. A morphometric analysis

BACKGROUND: Focal segmental glomerulosclerotic lesion (FSGS lesion) is frequently observed in preeclamptic patients with nephrotic syndrome. PATIENTS AND METHODS: We performed a morphometric analysis of renal biopsies from 20 patients with severe preeclampsia to evaluate the pathogenetic role of glomerular hypertrophy in preeclamptic nephropathy associated with FSGS lesion. We also analyzed biopsies obtained from 6 preeclamptic patients without FSGS lesion and 10 patients with isolated hematuria. Nonsclerotic glomeruli were examined. RESULTS: The mean glomerular tuft area (GTA), the whole glomerular area (WGA), and the extracellular matrix area (EMA) were significantly and negatively correlated with the postpartum day at biopsy in preeclamptic patients with FSGS lesion who underwent renal biopsy within 40 days after delivery. The mean GTA, WGA, EMA and number of mesangial cells (MN) were significantly increased in preeclamptic patients with FSGS lesion compared with patients with isolated hematuria and compared with those without FSGS lesion when the biopsy time was matched between patients with and without FSGS lesion. The GTA and WGA were not different between preeclamptic patients without FSGS lesion and patients with isolated hematuria. CONCLUSION: These results support the assumption that glomerular hypertrophy that develops during severe toxemic pregnancy plays an important role in the pathogenesis of FSGS lesion and is reversible about 40 days after delivery.     

Anterior Transhepatic Approach for Isolated Resection of the Caudate Lobe of the Liver

RID=" ID=" <E5>Correspondence to:</E5> J. Yamamoto, M.D.     

The correlation between feed-intake cycle and nutritional zinc-deficient status in rats

The characteristic cyclic variation in feed intake of rats fed a Zn-deficient diet (Mills et al, Am J Clin Nutr 22: 1240-1249 (1969)) followed a Cosinor curve, as determined by computer analysis (Tamaki et al, Br J Nutr 73: 711-722 (1995)). The values of amplitude for the feed-intake cycle had a positive correlation to their own day-to-day variations and to the correlation value of their own simulated cycles (r2 = 0.764, df = 50, p < 0.001 and r2 = 0.682, df = 50, p < 0.001, respectively). The cyclic variation in feed intake was accompanied by a cyclic variation in body-weight change in rats fed the Zn-deficient diet, and cyclic variation in body-weight change occurred similarly in pair-fed control rats. There were no differences in the mesors of body-weight change cycles of Zn-deficient rats and pair-fed control rats (Zn-deficient rats: 2.5 +/- 1.0 g/d, pair-fed rats: 2.8 +/- 1.0 g/d, mean +/- SD, df = 18, t = -0.674, ND). Rats fed the Zn-deficient diet were given different amounts of Zn supplementation by daily subcutaneous injection. The amplitude of the feed-intake cycle was decreased with increasing Zn supplementation (r2 = 0.919, df = 5, p < 0.001). The concentration of Zn for the appearance of the feed-intake cycle was estimated to be 71.6 +/- 6.6 micrograms/d per rat. The Zn level in the serum showed a significant decrease in the Zn-deficient diet groups, but the supplement of Zn did not vary in the Zn-deficient rats injected with up to 47.3 micrograms/d per rat. From these results, an analysis of the feed-intake cycle allowed us to estimate the quantitative Zn-deficient status of rats.     

Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and secretions of apolipoprotein B-containing lipoprotein and bile acids in HepG2

We studied the effect of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl) ureido]methyl]cyclohexane), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on intracellular cholesterol esterification and the secretion of apolipoprotein B100 (apoB)-containing lipoprotein and bile acids in the human hepatoma cell line HepG2. NTE-122 markably inhibited [3H]oleate incorporation into cholesteryl esters in HepG2 cells incubated with 5 microg/ml 25-hydroxycholesterol as a stimulus for ACAT (IC50=6.0 nM). On the other hand, NTE-122 did not affect [3H]oleate incorporation into triglycerides and phospholipids and [14C]acetate incorporation into cholesterol. The stimulation of ACAT by 25-hydroxycholesterol caused significant increases in the secretion of radiolabeled cholesteryl esters, radiolabeled triglycerides and apoB mass. NTE-122 pronouncedly inhibited the secretion of radiolabeled cholesteryl esters in proportion to the inhibition of cellular cholesterol esterification, and it significantly reduced the secretion of radiolabeled triglycerides and apoB mass in HepG2 cells incubated with 25-hydroxycholesterol. Furthermore, NTE-122 increased the secretion of bile acids synthesized from [14C]-cholesterol. These results suggest that NTE-122 is capable of exhibiting anti-hyperlipidemic effects by reducing both the cholesterol content and the amount of secreted very low-density lipoprotein and enhancing the excretion of bile acid from the liver.     

Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and high-density lipoprotein-induced cholesterol efflux in macrophages

We investigated the effects of a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), on ACAT activities in macrophages originating from several species and high-density lipoprotein (HDL)-induced cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells. NTE-122 inhibited cell-free ACAT activities in human PMA-treated THP-1 cells and mouse J774.1 cells with IC50 values of 0.88 and 360 nM, respectively. NTE-122 competively inhibited the ACAT activity in PMA-treated THP-1 cells. NTE-122 also inhibited cellular ACAT activities in PMA-treated THP-1 cells, rat peritoneal macrophages and J774.1 cells with IC50 values of 3.5, 84 and 6800 nM, respectively. Furthermore, NTE-122 prevented cholesterol accumulation in PMA-treated THP-1 cells incubated with acetylated low density lipoprotein, simultaneously with HDL, while it caused accumulation of a significant amount of free cholesterol in the absence and even in the presence of HDL. NTE-122 also enhanced HDL-induced cholesterol efflux from established foam cells converted from PMA-treated THP-1 cells. These results suggest that NTE-122, capable of inhibiting macrophage ACAT activity in humans more strongly than those in the other species, exhibits anti-atherogenic effects by preventing the foam cell formation and enhancing the foam cell regression in humans.     

Seasonal variation of saponins, sucurose and monosaccharides in cultivated ginseng roots

Yield of methanolic extract of fresh roots of Ginseng harvested in winter was found to be more than two-fold grater than from roots collected in summer; this remarkable increase is mainly due to the large increase of sucrose in roots in winter. On the other hand, biologically active dammarane-saponins in the roots increase in summer. These results indicate that roots should be harvested in summer for the production of high quality Ginseng extracts.